MEK Inhibitor 162 Relapsed and/or Refractory Acute Myeloid Leukemia (AML) and Poor Prognosis, Not Suitable for or Unwilling to Receive Standard Therapy

NCT02089230 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 2013-0116NCI-2014-01518
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of Phase 1 of this clinical research study is to find the highest tolerable dose of MEK162 that can be given to patients with advanced leukemia. This is an investigational study. MEK162 is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drug is designed to work. Up to 57 patients total will take part in both phases of this study . All will be enrolled at MD Anderson. The goal of Phase 2 of this clinical research study is to learn if MEK162 can help to control AML in older patients with advanced leukemia. The safety of this drug will also be studied. This is an investigational study. MEK162 is not FDA approved or commercially available. It is currently being used for research purposes only. The study doctor can explain how the study drug is designed to work. Up to 57 patients total will take part in both phases of this study. All will be enrolled at MD Anderson.

Conditions

Leukemia

Keywords

Leukemia; Acute Myeloid Leukemia; AML; Advanced leukemias; Myelodysplastic syndrome; MDS; Acute lymphoblastic leukemia; ALL; Relapsed; Refractory; MEK 162

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of MEK 162 in Participants With Advanced Leukemias

  Maximum tolerated dose is the highest dose level in which \<2 patients of 6 develop dose limiting toxicity (DLT).

  28 days

Secondary Outcomes (1)

• Number of Participants With a Response

  Assessed after one 28-day cycle of treatment

Study Arms (3)

Phase I Cohort 1 - MEK 162

EXPERIMENTAL

Phase I Starting Dose of MEK 162: 30 mg by mouth twice a day in a 28 day cycle.

Drug: MEK 162

Phase I Cohort 2 - MEK 162

EXPERIMENTAL

Phase I Starting Dose of MEK 162: 45 mg by mouth twice a day in a 28 day cycle.

Drug: MEK 162

Phase II Cohort 3 - MDK 162

EXPERIMENTAL

Phase II Starting Dose of MEK 162: 45 mg by mouth twice a day in a 28 day cycle.

Drug: MEK 162

Interventions

MEK 162 DRUG

Phase I Starting Dose of MEK 162: 15 mg by mouth twice a day in a 28 day cycle. Phase II Starting Dose of MEK 162: Maximum tolerated dose from Phase I.

Phase I Cohort 1 - MEK 162; Phase I Cohort 2 - MEK 162; Phase II Cohort 3 - MDK 162

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• PHASE I -- a. Primary or secondary AML according to World Health Organization (WHO) classification, with relapsed or refractory disease or newly diagnosed older subjects (greater than or equal to 65 years of age), not candidates for intensive chemotherapy; b. Subjects with MDS, International Prognostic Scoring System (IPSS) Int-2 or high risk (RAEB-2 only, i.e. greater than or equal to 10% blast) who are resistant or intolerant to standard treatment and are not candidates for transplantation; c. Subjects with ALL, relapsed, refractory or intolerant to standard treatment and for whom no effective treatment options are available.
• Age greater or equal to 18 years.
• Patients should be willing and able to give informed consent.
• Eastern Cooperative Group (ECOG) PS less than or equal to 2.
• PHASE II -- Patients aged 60 and older with newly diagnosed primary or secondary AML according to WHO classification, without any prior therapy for AML with the exception of (a) emergency Leukapheresis and (b) emergency treatment for hyperleukocytosis with hydroxyurea that is allowed until 24 hours before start of the trial treatment. Note: Prior therapy for preexisting hematological condition e.g. MDS or Myeloproliferative Disorder (MPD), including but not limited to hypomethylating agents is allowed until at least 2 weeks have elapsed from completion of that agent before the first dose of MEK 162.
• Patients must meet at least one of the following conditions: a. Age greater than or equal to 75 years; b. Age greater or equal to 60 and less than 75 years with at least one of the following poor prognostic factors: i. Secondary AML, as determined by known and documented exposure to chemotherapy or radiation therapy; ii. antecedent history of MDS or myeloproliferative disorder according to WHO criteria for at least 3 months prior to trial entry; iii. unfavorable cytogenetic abnormalities including chromosome 5 and 7 as well as complex; iv. ECOG Performance status 2. (Phase II ONLY)
• Patients are willing and able to give informed consent. (Phase II only)
• Only patients with mutated RAS (KRAS and NRAS) mutations are eligible to participate. (Phase II only)
• Adequate cardiac function defined as: --left ventricular ejection fraction (LVEF) greater than or equal to 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram; -- QTcF interval less than or equal to 480 ms. (Phase II only)

You may not qualify if:

• PHASE I and II -- Administration of any antineoplastic therapy within at least 4 weeks (cytotoxic chemotherapy) or 2 weeks (biological and targeted therapy; hypomethylating agents are considered to be biological therapy) of that therapy of the first MEK 162/MEK 162 dose; except the use of hydroxyurea which can be administered up to 5 g/day up to 24 hours before the initiation of the study drug.
• Patients should not have received an investigational agent for at least 2 weeks prior to the first study drug dose.
• Clinical evidence of active Central Nervous System (CNS) leukemia requiring active therapy; prior CNS leukemia well-controlled by ongoing therapy is allowed.
• Active and uncontrolled infection including but not limited to known infection with HIV, active hepatitis B, or hepatitis C.
• Major surgery within two weeks prior to trial entry.
• Liver function tests above the following limits at the screening: total bilirubin \> 1.5 x Upper Limit of Normal (ULN) unless related to Gilbert's syndrome or hemolysis, AST and/or ALT \> 2.5 X ULN, or for subjects with liver involvement Aspartate Aminotransferase (AST) and/or Alanine transaminase (ALT) \> 5 x ULN.
• Serum creatinine \> 1.5 x ULN and/or Creatinine Clearance (CrCl) \< 30 mL/min at screening (calculation according to Cockcroft \& Gault formula).
• Pregnant or nursing (lactating) women;
• Female patients of childbearing potential and male patients with partners of childbearing potential who are not willing ot use highly effective methods of contraception throughout the study and for 1 month after study drug discontinuation. Highly effective contraception methods include: \*\*Total abstinence; or \*\*Male or female sterilization; \*\*Combination of any two of the following (a+b or a+c or b+c); a. Use of oral, injected, or implanted hormonal methods of contraception; b. Placement of an intrauterine device (IUD) or intrauterine system (IUS); c. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository.
• Female patients with reproductive potential who do not have a negative blood or urine pregnancy test at screening;
• History of significant difficulty swallowing, malabsorption or other chronic gastro-intestinal disease or conditions that may hamper compliance and/or absorption of the tested product.
• Has significant cardiac conduction abnormalities and/ or pacemaker or any of the following criteria: -- History of acute coronary syndromes (including myocardial infarction, unstable angina, Coronary Artery Bypass Grafting (CABG), coronary angioplasty, or stenting) \<6 months prior to screening, --Symptomatic chronic heart failure; evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities \< 6 months prior to screening --Uncontrolled arterial hypertension, defined as BP \> 140/100 mmHg (average of 3 consecutive readings)
• History or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO).
• Any ophthalmopathy visible at screening that would be considered a risk factor for CSR or RVO by the ophthalmologist (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, history of hyperviscosity or hypercoagulability syndromes).
• Subjects with active other tumors, except early stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or cervical intraepithelial neoplasia (CIN).

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Array BioPharma: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Recurrence

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Farhad Ravandi-Kashani MD/Professor
• Organization: The University of Texas MD Anderson Cancer Center

fravandi@mdanderson.org

713-745-0394

Study Officials

• Farhad Ravandi-Kashani, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2014
• First Posted: March 17, 2014
• Study Start: August 27, 2014
• Primary Completion: June 5, 2019
• Study Completion: June 5, 2019
• Last Updated: April 20, 2021
• Results First Posted: April 20, 2021

Record last verified: 2021-03

Locations

US (1)